Prescribing lithium safely: side effects Flavio Guzman, MD

Overview

Side effects: classification Lithium toxicity Long-term Short-term (Acute)

Acute side effects

Acute side effects Within the first 5 days of starting lithium treatment Some of them are dose-related Transitory nature Ferrier, I. N., S. P. Tyrer, and A. J. Bell. "Lithium therapy." Advances in Psychiatric Treatment 1.4 (1995): 102-108.

Acute side effects Gastrointestinal: Metallic taste CNS: Abdominal discomfort Diarrhea Nausea Metallic taste CNS: Fine tremor Cognitive dulling Dysarthria Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

Acute renal side effects Renal: difficulty concentrating urine Lithium inhibits the effects of ADH ADH promotes the expression of aquaporin channels McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

H20 H20 H20 H20 H20

H20 H20 H20 H20 H20 H20

Acute renal side effects Thirst Polydipsia Polyuria

Acute renal side effects Thirst Polydipsia Polyuria Reversible Complications avoided by maintaining an adequate fluid and salt intake Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

Acute side effects: clinical considerations Dose related: Nausea Tremor Cognitive dulling May diminish Dose reduction Dividing the daily dose Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

Long-term effects

Renal: GFR, urine concentration Long-term effects Renal: GFR, urine concentration Hypothyroidism Hyperparathyroidism Weight gain Other: Cardiac (ECG changes) Dermatologic

Renal effects of lithium Glomerular filtration rate is impaired with lithium therapy Impairment is not clinically significant in most patients McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Renal effects of lithium Risk of end-stage renal failure Increased, but absolute risk is very low Risk of end-stage renal failure Healthy controls Bipolar patients on lithium 0.2 % 0.53 % McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Renal effects of lithium In most patients the trajectory of decrease of GFR is similar to that associated with ageing Diabetes more common in bipolar patients McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Hypothyroidism 8 - 19% of patients on lithium Especially in: Women Elderly Most patients are asymptomatic: biochemical diagnosis Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Thyroid 4 potential negative effects on thyroid function: Inhibition of iodine uptake Inhibition of iodotyrosine coupling Alteration in thyroglobulin structure Inhibition of thyroxine secretion 4 potential negative effects on thyroid function: McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Thyroid - UTD T3 I- T4

Thyroid - UTD T3 I- T4

Parathyroid – Primary hyperparathyroidism Frequent finding Lithium: absolute risk 10% General population 0.1% PTH Ca++ McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Thyroid and Parathyroid Thyroid and parathyroid abnormalities occur in about 25% of patients receiving lithium therapy Guidelines for bipolar disorder make no mention of monitoring of calcium. McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Weight gain Long-term treatment with lithium results in noticeable weight gain Reported by 5% or more of patients Important cause of nonadherence Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Weight gain Increase of 1-2 kg over the first 12 weeks of treatment is common In some patients this increase may continue Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Weight gain Important to anticipate weight gain: Preventive lifestyle changes: diet and exercise Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Weight gain – Factors Stimulation of hypothalamic center Hypothyroidism Increased thirst Insulin-like properties Weight gain McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

Fine Tremor Relatively common It occurs at therapeutic levels Common cause of treatment discontinuation Image credit: University of Miami Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Flapping or coarse tremor Fine Tremor Fine tremor Flapping or coarse tremor Image credit: University of Miami Malhi

Cardiac effects ECG changes QTc interval prolongation Increased PR interval duration Diffuse T-wave inversion Synus bradycardia Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Cardiac effects Most changes are reversible (disappear when lithium is withdrawn) Rarely may precipitate clinically significant arrhythmias Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3), 192-211.

Dermatologic side effects Acne Psoriasis Exacerbation of pre-existing psoriasis Induction of new lesions Kim, Grace K., and James Q. Del Rosso. "Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance." The Journal of clinical and aesthetic dermatology 3.1 (2010): 32.

End of presentation